((S)-2-((S)-2-((S)-2-amino-3-phenylpropanamido)-3-(benzyloxy)propanamido)-3-cyclohexylpropanoyl)-D-valyl-D-phenylalanine | 1252661-22-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ((S)-2-((S)-2-((S)-2-amino-3-phenylpropanamido)-3-(benzyloxy)propanamido)-3-cyclohexylpropanoyl)-D-valyl-D-phenylalanine
• CAS: 1252661-22-5
• 化学式: C₄₂H₅₅N₅O₇
• 分子量: 741.928
• InChiKey: PGAJEDJBBCQYJN-OCDDULBKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  54.0
• 可旋转键数：
  20.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  188.95
• 氢给体数：
  6.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ((S)-2-((S)-2-((S)-2-amino-3-phenylpropanamido)-3-(benzyloxy)propanamido)-3-cyclohexylpropanoyl)-D-valyl-D-phenylalanine 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 以5.1%的产率得到
  参考文献：
  名称：

  Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives

  摘要：

  Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.07.042
• 作为产物：
  描述：

  Fmoc-D-缬氨酸 、 Fmoc-D-苯丙氨酸 、 Fmoc-O-苄基-L-丝氨酸 、 FMOC-Β-环己基-L-丙氨酸 、 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以273 mg的产率得到((S)-2-((S)-2-((S)-2-amino-3-phenylpropanamido)-3-(benzyloxy)propanamido)-3-cyclohexylpropanoyl)-D-valyl-D-phenylalanine
  参考文献：
  名称：

  Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives

  摘要：

  Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.07.042